Wild-type p53 transmits signals from genotoxic stress to genes and factors that regulate cell growth and cell death. p53 mutation is a highly frequent event inmany of the major forms of human cancer. In at least half of these tumors, mutant forms of p53 protein are expresssed, frequently at high levels. Despite the advanced level of understanding of the structure and functions of the normal, wild-type form of p53 protein, there is still much to learn about the properties of tumor- derived mutant forms of p53. The goals of the proposed research are to study the "hot spot" mutant proteins in terms of their structural charactertistics, modifications and DNA binding properties. It is planned to examine and screen for ways to convert mutant p53 proteins to ones that are more wild-type in conformation. The attributes of mutant forms of p53 which confer prooncogenic properties upon cells will be examined. Finally, it is also intended to assess the impact of p53 status on the response of tumor cells to antineoplastic agents.